| Literature DB >> 25417109 |
Keisuke Okabe1, Sakiko Kobayashi2, Toru Yamada3, Toshihide Kurihara4, Ikue Tai-Nagara2, Takeshi Miyamoto5, Yoh-suke Mukouyama6, Thomas N Sato7, Toshio Suda8, Masatsugu Ema9, Yoshiaki Kubota10.
Abstract
Vascular and nervous systems, two major networks in mammalian bodies, show a high degree of anatomical parallelism and functional crosstalk. During development, neurons guide and attract blood vessels, and consequently this parallelism is established. Here, we identified a noncanonical neurovascular interaction in eye development and disease. VEGFR2, a critical endothelial receptor for VEGF, was more abundantly expressed in retinal neurons than in endothelial cells, including endothelial tip cells. Genetic deletion of VEGFR2 in neurons caused misdirected angiogenesis toward neurons, resulting in abnormally increased vascular density around neurons. Further genetic experiments revealed that this misdirected angiogenesis was attributable to an excessive amount of VEGF protein around neurons caused by insufficient engulfment of VEGF by VEGFR2-deficient neurons. Moreover, absence of neuronal VEGFR2 caused misdirected regenerative angiogenesis in ischemic retinopathy. Thus, this study revealed neurovascular crosstalk and unprecedented cellular regulation of VEGF: retinal neurons titrate VEGF to limit neuronal vascularization. PAPERFLICK:Entities:
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Year: 2014 PMID： 25417109 DOI： 10.1016/j.cell.2014.09.025
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582